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VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma

Neuroblastoma (NB) is a childhood cancer with a low survival rate and great metastatic potential. Vascular endothelial growth factor (VEGF), an angiogenesis factor, has been found to be involved in CRT-related neuronal differentiation of NB cells. In this study, we further confirmed the role VEGF in...

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Autores principales: Weng, Wen-Chin, Lin, Kuan-Hung, Wu, Pei-Yi, Ho, Ya-Hsuan, Liu, Yen-Lin, Wang, Bo-Jeng, Chen, Chien-Chin, Lin, Yueh-Chien, Liao, Yung-Feng, Lee, Wang-Tso, Hsu, Wen-Ming, Lee, Hsinyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593816/
https://www.ncbi.nlm.nih.gov/pubmed/28894229
http://dx.doi.org/10.1038/s41598-017-11637-8
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author Weng, Wen-Chin
Lin, Kuan-Hung
Wu, Pei-Yi
Ho, Ya-Hsuan
Liu, Yen-Lin
Wang, Bo-Jeng
Chen, Chien-Chin
Lin, Yueh-Chien
Liao, Yung-Feng
Lee, Wang-Tso
Hsu, Wen-Ming
Lee, Hsinyu
author_facet Weng, Wen-Chin
Lin, Kuan-Hung
Wu, Pei-Yi
Ho, Ya-Hsuan
Liu, Yen-Lin
Wang, Bo-Jeng
Chen, Chien-Chin
Lin, Yueh-Chien
Liao, Yung-Feng
Lee, Wang-Tso
Hsu, Wen-Ming
Lee, Hsinyu
author_sort Weng, Wen-Chin
collection PubMed
description Neuroblastoma (NB) is a childhood cancer with a low survival rate and great metastatic potential. Vascular endothelial growth factor (VEGF), an angiogenesis factor, has been found to be involved in CRT-related neuronal differentiation of NB cells. In this study, we further confirmed the role VEGF in NB through mouse xenograft model and clinical analysis from NB patients. In xenograft experiments, CRT overexpression effectively inhibited the tumor growth. In addition, the mRNA and protein levels of VEGF and differentiation marker GAP-43 were upregulated by induced CRT expression. However, no significant correlation between the expression level of VEGF and microvessel density was observed in human NB tumors, suggesting a novel mechanism of VEGF participating in NB tumorigenesis through an angiogenesis-independent pathway. In NB patients’ samples, mRNA expression levels of CRT and VEGF were positively correlated. Furthermore, positive VEGF expression by immunostaining of NB tumors was found to correlate well with histological grade of differentiation and predicted a favorable prognosis. In conclusion, our findings suggest that VEGF is a favorable prognostic factor of NB and might affect NB tumor behavior through CRT-driven neuronal differentiation rather than angiogenesis that might shed light on a novel therapeutic strategy to improve the outcome of NB.
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spelling pubmed-55938162017-09-13 VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma Weng, Wen-Chin Lin, Kuan-Hung Wu, Pei-Yi Ho, Ya-Hsuan Liu, Yen-Lin Wang, Bo-Jeng Chen, Chien-Chin Lin, Yueh-Chien Liao, Yung-Feng Lee, Wang-Tso Hsu, Wen-Ming Lee, Hsinyu Sci Rep Article Neuroblastoma (NB) is a childhood cancer with a low survival rate and great metastatic potential. Vascular endothelial growth factor (VEGF), an angiogenesis factor, has been found to be involved in CRT-related neuronal differentiation of NB cells. In this study, we further confirmed the role VEGF in NB through mouse xenograft model and clinical analysis from NB patients. In xenograft experiments, CRT overexpression effectively inhibited the tumor growth. In addition, the mRNA and protein levels of VEGF and differentiation marker GAP-43 were upregulated by induced CRT expression. However, no significant correlation between the expression level of VEGF and microvessel density was observed in human NB tumors, suggesting a novel mechanism of VEGF participating in NB tumorigenesis through an angiogenesis-independent pathway. In NB patients’ samples, mRNA expression levels of CRT and VEGF were positively correlated. Furthermore, positive VEGF expression by immunostaining of NB tumors was found to correlate well with histological grade of differentiation and predicted a favorable prognosis. In conclusion, our findings suggest that VEGF is a favorable prognostic factor of NB and might affect NB tumor behavior through CRT-driven neuronal differentiation rather than angiogenesis that might shed light on a novel therapeutic strategy to improve the outcome of NB. Nature Publishing Group UK 2017-09-11 /pmc/articles/PMC5593816/ /pubmed/28894229 http://dx.doi.org/10.1038/s41598-017-11637-8 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Weng, Wen-Chin
Lin, Kuan-Hung
Wu, Pei-Yi
Ho, Ya-Hsuan
Liu, Yen-Lin
Wang, Bo-Jeng
Chen, Chien-Chin
Lin, Yueh-Chien
Liao, Yung-Feng
Lee, Wang-Tso
Hsu, Wen-Ming
Lee, Hsinyu
VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma
title VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma
title_full VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma
title_fullStr VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma
title_full_unstemmed VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma
title_short VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma
title_sort vegf expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593816/
https://www.ncbi.nlm.nih.gov/pubmed/28894229
http://dx.doi.org/10.1038/s41598-017-11637-8
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